Could Vioxx cousin prevent religious fast headache?

NEW YORK (Reuters Health) - Every year, millions of observant Jews fast on their holiest day, Yom Kippur, and millions of Muslims fast for the month of Ramadan. And every year, as many as 40 percent of those who fast develop serious headaches.

But given the prohibitions against taking anything by mouth, there's little these observers can do until the fast ends - nightly for Muslims, and after 25 hours for Jews.

Now, a team of researchers in Israel, reporting in the journal Headache, thinks they have a solution: A cousin of Vioxx (rofecoxib), the drug Merck pulled from the U.S. market in September 2004 because it increased the risks of heart attacks and other serious complications.

The drug, etoricoxib (Arcoxia), is also made by Merck, and it's approved in several European countries, as well as Israel. Because it works the same way Vioxx does, the FDA refused to approve it in the U.S. in 2007.

Dr. Michael Drescher, of Hartford Hospital, Connecticut, and colleagues at two hospitals in Israel recruited more than 200 volunteers before Yom Kippur in October 2008. Just before the holiday, half of them took etoricoxib, and half were given inactive placebo pills. Neither the volunteers nor the researchers knew which was which until after the study.

Among the 195 study participants who responded to a survey after the holiday, about 36 percent who took etoricoxib developed headaches, compared to about 68 percent who took the inactive placebo. Those who took etoricoxib also had less severe headaches, and they had an easier time fasting.

Yom Kippur headache is a well documented phenomenon, even in the medical literature, including a 1995 paper in the journal Neurology. The causes are unclear, but doctors have suspected withdrawal from caffeine, nicotine, oversleeping, and dehydration.

The fast, however, "doesn't allow people to start taking medicines," Drescher told Reuters Health. "There are different folk remedies, including suppositories, but really no good solution."

In fact, there is an entire book on the subject of how to treat medical conditions during Yom Kippur, noted Dr. Edward Reichman, an associate professor of emergency medicine at the Albert Einstein College of Medicine in the Bronx, New York, and a rabbi and medical ethicist. An April 2008 paper in the journal Endocrine Practice, for example, described how doctors should manage their diabetic observant Jewish patients' blood sugars on Yom Kippur, because a fast obviously leads to significant swings.

Because of the 25-hour fast, Drescher's team knew they needed a headache drug that wouldn't wear off quickly. Most painkillers only last for 12 hours, or less, but Yom Kippur headache usually kicks in at about 15 or 16 hours. That led Drescher and a colleague to Vioxx, which has what scientists refer to as a long half-life - 17 hours - that means it acts longer.

Before they did a study, however, they asked "every credible rabbinical source" they could find whether taking a drug to prevent headaches would be in the spirit of the fast. (Their study cites the Biblical book of Leviticus, for example.)

They said it was, to coin a phrase, kosher. "Rabbis told us it's not a matter of suffering," Drescher said. "It's about divorcing yourself from the day to day."

When they did a study of Vioxx during Yom Kippur in September 2004, they saw similar results to those in the current report. But within days of the earlier study, Merck pulled the drug from the market. Drescher said his team later published the results, also in the journal Headache, but the withdrawal "was a blow."

So the researchers came upon etoricoxib, which Drescher said has an even longer half-life. They were very pleased with the results in the current study.

The fact that a fasting headache is such a widespread problem, without an easy solution, could explain why the survey response rate - above 90 percent -- was so much higher than usual, said Reichman, who was not involved in the study. (That could also explain why 68 percent of those who received placebo had headaches, which is more than other studies have seen; this could be a group that knew they were likely to have headaches.) The researchers also used text messages to remind participants to take the drug before beginning the fast, and to answer the survey at the end.

"It's a simple yet elegant study," Reichman told Reuters Health. "It's very well-done, and addresses a need in the community."

Drescher said that with the risks of Vioxx in mind, the researchers were careful to only include healthy non-elderly people in their study. Doctors should take such risks into account before prescribing etoricoxib, he said, but one-time use of etoricoxib would be unlikely to be linked to the serious problems seen with long-term Vioxx use.

One of the paper's authors, Dr. Rafael Torgovicky, works for Merck Sharpe & Dohme Israel, a Merck subsidiary that funded the study.

Drescher has already applied for a grant for his next project: Figuring out whether etoricoxib will work for Ramadan headaches.